Activating transcription factor 4 (ATF4) is upregulated by human herpesvirus 8 infection, increases virus replication and promotes proangiogenic properties
Activating transcription factor 4 (ATF4) is upregulated by human herpesvirus 8 infection, increases virus replication and promotes proangiogenic properties
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DOI：
10.1007/s00705-011-1144-3
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发表时间：
2012-01-01
影响因子：
2.7
通讯作者：
Di Luca, Dario
中科院分区：
文献类型：
--
作者：
Caselli, Elisabetta;Benedetti, Sabrina;Di Luca, Dario
人疱疹病毒8型（HHV-8）通过激活核因子κ B（NF-κ B）诱导单核细胞趋化蛋白1（MCP-1）而触发内皮细胞中的促血管生成行为。然而，NF-κ B抑制仍然导致部分MCP-1诱导和随后的血管生成，表明另一个转录途径的参与。我们分析了激活转录因子4（ATF 4），因为它是细胞应激反应的中心，并参与血管生成。结果显示，HHV-8上调ATF 4表达，这反过来促进HHV-8感染，并诱导内皮细胞中MCP-1产生和促血管生成特性。相比之下，ATF 4沉默减少病毒复制并抑制病毒诱导的MCP-1产生和管状结构的诱导。因此，ATF 4在HHV-8复制和相关病毒诱导的血管生成中发挥作用。阐明参与这一过程的分子途径将导致更好地了解病毒诱导的血管生成过程，并可能有助于设计新的治疗方法，以减少肿瘤的生长。
Human herpesvirus 8 (HHV-8) triggers proangiogenic behaviour in endothelial cells by inducing monocyte chemoattractant protein 1 (MCP-1) through activation of Nuclear Factor kappa B (NF-kappa B). However, NF-kappa B inhibition still results in partial MCP-1 induction and consequent angiogenesis, suggesting the involvement of another transcriptional pathway. We analysed activating transcription factor 4 (ATF4), since it is central in the cellular response to stress and is involved in angiogenesis. The results show that HHV-8 upregulates ATF4 expression, which in turn promotes HHV-8 infection, and induces MCP-1 production and proangiogenic properties in endothelial cells. By contrast, ATF4 silencing decreases virus replication and inhibits virus-induced MCP-1 production and induction of tube-like structures. Therefore, ATF4 plays a role in HHV-8 replication and associated virus-induced angiogenesis. The elucidation of molecular pathways involved in this process will result in a better understanding of the virus-induced angiogenic process and might help in designing novel therapies to reduce tumour growth.